Polysaccharide Meets Polyoxazoline: Regio- and Stereodefined β-1,2-Linked Pseudo-polysaccharides via Controlled...

Polysaccharides exhibit remarkable stereochemical and regiochemical complexity, yet their natural heterogeneity produces differences in composition and material behavior that are difficult to control or predict. Here, we report a synthetic approach that overcomes these challenges through the controlled, cationic ring-opening polymerization of glucosamine-derived 2-oxazoline monomers, affording a new class of well-defined pseudo-polysaccharides, wherein each saccharide subunit is 1,2-N-linked through a nitrogen containing a pendant acyl group. Under optimized conditions using a benzyl-protected monomer (OBn-GlcOx) and a methyl tosylate initiator, polymerization proceeds to full conversion within 3 h at 75 °C with linear molecular weight growth, first-order kinetics, and low dispersity (D̵ ≤ 1.2), consistent with a controlled polymerization mechanism. The resulting polymers exhibit complete β-1,2-regio- and stereoselectivity, narrow molecular-weight distributions, and retention of chain-end functionality that enables chain extension to form diblock copolymers with 2-methyl-2-oxazoline. Following quantitative deprotection, the resulting polymer is water-soluble and both protected and nonprotected versions display markedly enhanced resistance to ultrasonic, acidic, and thermal degradation as compared to chitosan (mass loss ≤63% vs 93% under harshest conditions). These findings establish a synthetic route to stereoregular, amide-linked pseudo-polysaccharides with tunable physicochemical properties, expanding the accessible design space for well-defined, carbohydrate-based materials.